Glycopyrrolate, like other anticholinergic (antimuscarinic) agents, inhibits the action of acetylcholine on structures innervated by postganglionic cholinergic nerves and on smooth muscles that respond to acetylcholine by lack cholinergic innervation. These peripheral cholinergic receptors are present in the autonomic effector cells of smooth muscle, cardiac muscle, the sino-atrial node, the atrioventricular node, exocrine glands, and, to a limited degree, in the autonomic ganglia. Thus, it diminishes the volume and free acidity of gastric secretions and controls excessive pharyngeal, tracheal, and bronchial secretions.
Glycopyrrolate antagonizes muscarinic symptoms (e.g., bronchorrhea, bronchospasm, bradycardia, and intestinal hypermotility) induced by cholinergic drugs such as the anticholinesterases.
The highly polar quaternary ammonium group of glycopyrrolate limits its passage across lipid membranes, such as the blood-brain barrier, in contrast to atropine sulfate and scopolamine hydrobromide, which are non-polar tertiary amines which penetrate lipid barriers easily.
INDICATIONS AND USAGE: For use as adjunctive therapy in the treatment of peptic ulcer.
Other: Adjunct in the treatment of PUD; inhibits salivation and excessive secretions of the respiratory tract preoperatively; reversal of neuromuscular blockade; control of upper airway secretions. Onset: Oral: with in 50 min; IM: 20-40min ; IV: 10-15min.
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-------------------------------------------------------------------------------------- Tablets: -------------------------------------------------------------------------------------- The dosage of Glycopyrrolate Tablets, USP should be adjusted to the needs of the individual patient to assure symptomatic controlwith a minimum of adverse reactions. The presently recommended maximum daily dosage of glycopyrrolate is 8 mg.
Glycopyrrolate Tablets, USP 1 mg. The recommended initial dosage of Glycopyrrolate 1 mg tablets for adults is one tablet three times daily (in the morning, early afternoon, and at bedtime). Some patients may require two tablets at bedtime to assure overnight control of symptoms.
For maintenance, a dosage of one tablet twice a day is frequently adequate.
Glycopyrrolate Tablets, USP 2 mg. The recommended dosage of Glycopyrrolate 2 mg tablets for adults is one tablet two or three times daily at equally spaced intervals.
Glycopyrrolate Tablets, USP 1.5 mg. The Glycopyrrolate 1.5 mg tablets may be used to provide intermediate titration doses based on response of the patient.
Glycopyrrolate Tablets, USP are not recommended for use in pediatric patients under the age of 12 years. -------------------------------------------------------------------------------------- Injection: NOTE: CONTAINS BENZYL ALCOHOL -------------------------------------------------------------------------------------- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Glycopyrrolate Injection may be administered intramuscularly, or intravenously, without dilution, in the following indications.
Adults Preanesthetic Medication The recommended dose of Glycopyrrolate Injection is 0.004 mg/kg by intramuscular injection, given 30 to 60 minutes prior to the anticipated time of induction of anesthesia or at the time the preanesthetic narcotic and/or sedative are administered.
Intraoperative Medication Glycopyrrolate Injection may be used during surgery to counteract drug-induced or vagal reflexes and their associated arrhythmias (e.g., bradycardia). It should be administered intravenously as single doses of 0.1 mg and repeated, as needed, at intervals of 2 to 3 minutes. The usual attempts should be made to determine the etiology of the arrhythmia, and the surgical or anesthetic manipulations necessary to correct parasympathetic imbalance should be performed.
Reversal of Neuromuscular Blockade The recommended dose of Glycopyrrolate Injection is 0.2 mg for each 1.0 mg of neostigmine or 5.0 mg of pyridostigmine. In order to minimize the appearance of cardiac side effects, the drugs may be administered simultaneously by intravenous injection and may be mixed in the same syringe.
Peptic Ulcer The usual recommended dose of Glycopyrrolate Injection is 0.1 mg administered at 4-hour intervals, 3 or 4 times daily intravenously or intramuscularly. Where more profound effect is required, 0.2 mg may be given. Some patients may need only a single dose, and frequency of administration should be dictated by patient response up to a maximum of four times daily.
Glycopyrrolate Injection is not recommended for the treatment of peptic ulcer in pediatric patients .
Pediatric Patients (see PRECAUTIONS - Pediatric Use)
Preanesthetic Medication The recommended dose of Glycopyrrolate Injection in pediatric patients is 0.004 mg/kg intramuscularly, given 30 to 60 minutes prior to the anticipated time of induction of anesthesia or at the time the preanesthetic narcotic and/or sedative are administered.
Infants (1 month to 2 years of age) may require up to 0.009 mg/kg.
Intraoperative Medication Because of the long duration of action of Glycopyrrolate Injection if used as preanesthetic medication, additional Glycopyrrolate Injection for anticholinergic effect intraoperatively is rarely needed; in the event it is required the recommended pediatric dose is 0.004 mg/kg intravenously, not to exceed 0.1 mg in a single dose which may be repeated, as needed, at intervals of 2 to 3 minutes. The usual attempts should be made to determine the etiology of the arrhythmia, and the surgical or anesthetic manipulations necessary to correct parasympathetic imbalance should be performed.
Reversal of Neuromuscular Blockade The recommended pediatric dose of Glycopyrrolate Injection is 0.2 mg for each 1.0 mg of neostigmine or 5.0 mg of pyridostigmine. In order to minimize the appearance of cardiac side effects, the drugs may be administered simultaneously by intravenous injection and may be mixed in the same syringe.
Peptic Ulcer Glycopyrrolate Injection is not recommended for the treatment of peptic ulcer in pediatric patients (see PRECAUTIONS – Pediatric Use).
Diluent Compatibilities Dextrose 5% and 10% in water, or saline, dextrose 5% in sodium chloride 0.45%, sodium chloride 0.9%, and Ringer’s Injection.
Diluent Incompatibilities Lactated Ringer’s solution
CONTRAINDICATIONS: Glaucoma; obstructive uropathy (for example, bladder neck obstruction due to prostatic hypertrophy); obstructive disease of the gastrointestinal tract (as in achalasia, pyloroduodenal stenosis, etc.); paralytic ileus; intestinal atony of the elderly or debilitated patient; unstable cardiovascular status in acute hemorrhage; severe ulcerative colitis; toxic megacolon complicating ulcerative colitis; myasthenia gravis. Glycopyrrolate tablets are contraindicated in those patients with a hypersensitivity to glycopyrrolate.
WARNINGS AND PRECAUTIONS: WARNINGS
In the presence of a high environmental temperature, heal prostration (fever and heat stroke due to decreased sweating) can occur with the use of Glycopyrrolate Tablets, USP.
Diarrhea may be an early symptom of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy. In this instance treatment with this drug would be inappropriate and possibly harmful.
Glycopyrrolate Tablets, USP may produce drowsiness or blurred vision. In this event, the patient should be warned not to engage in activities requiring mental alertness such as operating a motor vehicle or other machinery, or performing hazardous work while taking this drug.
Theoretically, with overdosage, a curare-like action may occur, i.e., neuro-muscular blockade leading to muscular weakness and possible paralysis.
PRECAUTIONS
Use Glycopyrrolate Tablets, USP with caution in the elderly and in all patients with:
• Autonomic neuropathy.
• Hepatic or renal disease.
• Ulcerative colitis - large doses may suppress intestinal motility to the point of producing a paralytic ileus and for this reason may precipitate or aggravate the "toxic megacolon," a serious complication of the disease.
• Hyperthyroidism, coronary heart disease, congestive heart failure, cardiac tachyarrhythmias, tachycardia, hypertension and prostatic hypertrophy.
• Hiatal hernia associated with reflux esophagitis, since anticholinergic drugs may aggravate this condition.
Precautions - Pediatric: Pediatric Use Due to its benzyl alcohol content, Glycopyrrolate Injection should not be used in neonates, i.e., patients less than 1 month of age.
Safety and effectiveness in pediatric patients below the age of 16 years have not been established.
Safety and effectiveness in pediatric patients have not been established for the management of peptic ulcer.
Dysrhythmias associated with the use of glycopyrrolate intravenously as a premedicant or during anesthesia have been observed in pediatric patients.
Infants, patients with Down’s syndrome, and pediatric patients with spastic paralysis or brain damage may experience an increased response to anticholinergics, thus increasing the potential for side effects.
A paradoxical reaction characterized by hyperexcitability may occur in pediatric patients taking large doses of anticholinergics including Glycopyrrolate Injection. Infants and young children are especially susceptible to the toxic effects of anticholinergics.
Benzyl alcohol, a component of this drug product, has been associated with serious adverse events and death, particularly in pediatric patients. The “gasping syndrome,” (characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with benzyl alcohol dosages >99 mg/kg/day in neonates and low-birth-weight neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hemotologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Although normal therapeutic doses of this product deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the “gasping syndrome,” the minimum amount of benzyl alcohol at which toxicity may occur is not known. Premature and low-birthweight infants, as well as patients receiving high dosages, may be more likely to develop toxicity. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources.
ADVERSE REACTIONS: Anticholinergics produce certain effects, most of which are extensions of their fundamental pharmacological actions. Adverse reactions to anticholinergics in general may include xerostomia; decreased sweating; urinary hesitancy and retention; blurred vision; tachycardia; palpitations; dilation of the pupil; cycloplegia; increased ocular tension; loss of taste; headaches; nervousness; mental confusion; drowsiness; weakness; dizziness; insomnia; nausea; vomiting; constipation; bloated feeling; impotence; suppression of lactation; severe allergic reaction or drug idiosyncrasies including anaphylaxis, urticaria and other dermal manifestations.
Glycopyrrolate Tablets, USP is chemically a quaternary ammonium compound; hence, its passage across lipid membranes, such as the blood-brain barrier, is limited in contrast to atropine sulfate and scopolamine hydrobromide. For this reason the occurrence of CNS related side effects is lower, in comparison to their incidence following administration of anticholinergics which are chemically tertiary amines that can cross this barrier readily.
DOSAGE FORMS AND STRENGTHS: Glycopyrrolate Tablets, USP 1.5 mg are compressed white tablets debossed GP on one side and 1.5 on the other and are supplied in bottles of 100 (NDC 0722-7097-01).
Injection: Glycopyrrolate Injection, USP, 0.2 mg/mL, is available in:
1 mL single dose vials packaged in 25s (NDC 10019-016-81)
2 mL single dose vials packaged in 25s (NDC 10019-016-17)
5 mL multiple dose vials packaged in 25s (NDC 10019-016-54)
20 mL multiple dose vials in 10s (NDC 10019-016-02)
SOURCE: Package insert data: |